The goal of this project is to determine the DNA sequence of Francisella tularensis subspecies holarctica, the causative agent of tularemia. F. tularensis has been classified as a Category A Select Agent posing a serious military and civilian bioterrorism threat. Two strains of F. tularensis are currently being sequenced: a highly virulent type A strain and a type B (holarctica) strain used as a live vaccine. This project will determine the sequence of the genome of the parent of the vaccine strain. This strain is expected to retain intact virulence factors that have been altered in the vaccine strain, leading to its attenuation. Thus comparison of this sequence with that of the live vaccine strain as well as the type A strain will identify candidate genes for virulence factors. Moreover, sera from vaccinated individuals should be useful in identifying antigens in future studies, using the genomic sequence of the type B strain. Early results from genomic studies suggest that F. tularensis contains a high proportion of unique genes compared to other bacterial genomes. Therefore, knowledge of the complete genome sequences of F. tularensis strains is needed for the understanding of the virulence mechanisms. [unreadable] [unreadable] [unreadable]